This invention relates to processes for producing the compound of formula (I) ##STR2## (hereinafter referred to as spirolaxine); and to processes for producing the compound of formula (II) ##STR3## (hereinafter referred to as spirolaxine methyl ether).
Spirolaxine is a known antibiotic which can be isolated from the fungus Chrysosporium pruinosum ATCC 15155. Spirolaxine is reported to have weak bacteriostatic activity against Bacillus cereus, Bacillus subtillis and Escherichia coli. Arnone et al., Phytochemistry, 1990, 29, 613-616. Further, spirolaxine is reported to have no antifungal activity against Aspergillus niger, Botrytis cinerea, Cladosporium, cucumerinum, Ophiostoma ulmi and Saccharomyces cerevisiae. Arnone et al., Phytochemistry, 1990, 29, 613-616.
Gastric and duodenal ulcers affect a significant portion of the human population worldwide. Currently, the usual treatment for both gastric and duodenal ulcers involves treatment of the patient with H.sub.2 blockers. While generally effective in healing ulcers, ulcer relapse occurs in up to 90% of patients within a year of discontinuing H.sub.2 blocker therapy. O'Connor, H. J., Postgraduate Medical Journal, 1992, 68, 549-57. Thus, patients must continue the treatment for many years or risk a recurrence of the ulcer. It is now known that ulcer healing drugs such as colloidal bismuth subcitrate (CBS) are helicobactericidal and as such CBS is used in combination with H.sub.2 blockers to treat ulcers. O'Connor, ibid. Additionally, CBS, an H.sub.2 blocker and amoxicillin have been used in combination to treat ulcer patients. O'Connor, ibid.
Helicobacter pylori has recently been demonstrated to be a major causative agent in gastric and duodenal ulcers and other gastroduodenal disorders, diseases and adverse conditions. Thus, antibiotic therapy to eliminate Helicobacter pylori from the gastroduodenal tract would remove the root cause of said gastroduodenal disorders, diseases and adverse conditions and eliminate the need for an ulcer patient to continue long and costly treatment with H.sub.2 blockers and the like. None of the foregoing treatments are capable of 100% eradication of Helicobacter pylori.
Spirolaxine and spirolaxine methyl ether are potent helicobactericidal compounds, as disclosed hereinbelow. A helicobactericidal compound is a compound which kills Helicobacter pylori. Therefore spirolaxine and spirolaxine methyl ether possess utility in treating gastroduodenal disorders, diseases and adverse conditions and particularly in treating gastric and duodenal ulcer and preventing gastric cancer.
It has now been found that spirolaxine and spirolaxine methyl ether are produced by various strains of fungi belonging to the genera Sporotrichum and Phanerochaete.